title: Exposure to ertapenem is possibly associated with Pseudomonas aeruginosa antibiotic resistance.
abstract: The role of antibiotic exposure in the evolution and emergence of resistance is challenging to assess. We used carbapenem-resistant Pseudomonas aeruginosa (PA) phenotypes to assess possible factors that are associated with the occurrence and prognosis of such a phenotype and to examine the possible contribution of antibiotic exposure to the evolution of antimicrobial resistance. We conducted a nested case-control study. Cases were defined as patients from whom carbapenem-resistant ureidopenicillin-sensitive PA (CRUS-PA) was isolated; matched controls were PA patients who did not have isolation of CRUS-PA. We analysed potential predictors of CRUS-PA isolation and assessed their clinical significance (mortality and eventual isolation of pan-resistant PA), taking into account antibiotic exposures. We matched 800 case-control pairs. Case patients were more likely to have been exposed to anti-PA carbapenems (OR = 6.9; 95% CI, 2.5-18.6). This finding did not apply to the administration of other antibiotics. The mortality among CRUS-PA patients was similar to that of the controls (HR, 0.8 95%; CI, 0.6-1.1). Subsequent isolation of pan-resistant PA was more frequent among case patients compared with non-pan-resistant controls (p-value <0.05). Among cases, the risk of eventual pan-resistant PA isolation was increased in ertapenem recipients, only after and not prior to the index specimen date (HR, 1.9, 95%; CI, 1.01-3.4). Therefore we suggest that the CRUS-PA phenotype may represent pan beta-lactam resistance and that antibiotic exposure is associated with evolution of PA resistance phenotypes. We demonstrate a novel association of ertapenem with sequentially appearing PA resistance patterns.
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Centers, Jerusalem, Israel.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cohen
authors.forename: C S
authors.initials: CS
authors.lastname: Block
authors.forename: A E
authors.initials: AE
authors.lastname: Moses
authors.forename: R
authors.initials: R
authors.lastname: Nir-Paz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D024881:Drug Resistance, Bacterial; D000077727:Ertapenem; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem
keywords: Carbapenem antibiotics; Pseudomonas aeruginosa; Resistance